To investigate the structure–activity relationship of coumarins for the inhibitory activity on mushroom tyrosinase, the 50% inhibitory concentration (IC50 values) of 18 coumarins and four cinnamic acid derivatives were measured. Among these compounds, esculetin had the strongest inhibitory activity (IC50=43 μM) on mushroom tyrosinase. Introduction of a hydroxy group to the C6 and C7 positions of the coumarin ring and no substitution on the lactone ring played an important role in the expression of the strong inhibitory activity of esculetin. We performed further studies to estimate the in vitro inhibitory effects of esculetin on melanogenesis. Esculetin 5 μM significantly suppressed melanin production in murine B16 melanoma cells without affecting cell growth. Furthermore, the number of 3,4-dihydroxyphenylalanine (DOPA)-positive melanocytes in the split-epidermal sheets treated with 0.05% or 0.1% esculetin was significantly lower than that in the control. From these results, it is suggested that esculetin has inhibitory effects on tyrosinase activity in vitro. However, further detailed studies are necessary to understand the inhibitory mechanism of esculetin.
Background: The Atkins diet modified for epilepsy patients (modified Atkins diet: MAD) was reported to be a substitute for the classical ketogenic diet. Recently, it has been shown that this diet is effective not only for intractable childhood epilepsy but also for intractable adulthood epilepsy and Glut 1 deficiency syndrome. In Japan, this diet is difficult to promote, because the menu and the taste are not suitable for Japanese and side effects of this unbalanced diet remain unclear.Methods: To promote this therapy in Japan, the recipes of MAD were modified to adapt to the Japanese population, and evaluated in 10 healthy adult volunteers for 1 week. Subjects' evaluation for taste and hunger, as well as urinary and blood laboratory examinations were analyzed.Results: All volunteers evaluated the diet menu as sufficiently palatable, and continued the diet without difficulty for 1 week. However, they felt uneasy with the fatty menu and complained of constipation that was within tolerable levels. As for urinary ketone bodies measured by ketostick, four and six volunteers were 2 to 4+ and 1 to 2+, respectively at the end of the trial. Side effects including variable degrees of weight loss, hypoglycemia, hypercholesterolemia, and hyperuricemia were observed in all subjects.Conclusion: MAD can be used more comfortably as a substitute for the classical ketogenic diet, if the recipes are adapted for Japanese population. The diet would result in a sufficient level of ketosis since our adult volunteers developed mild to moderate ketosis despite only one-week trial without starvation. The long-term side effects should be carefully monitored because even the short-term trial results in some metabolic changes.
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A tyrosinase inhibitor was isolated from the seeds of Euphorbia lathyris L. by bioassay-guided fractionation and purification, using silica gel column chromatography. It was identified as esculetin by comparing its physical properties and spectral data with those of an authentic sample. The IC50 value of esculetin in the mushroom tyrosinase activity test was 43 μM. The kinetic study indicates that esculetin exhibited competitive inhibition against the oxidation of 3-(3,4-dihydroxyphenyl)-alanine by mushroom tyrosinase. The structure-activity relationships among five esculetin analogs suggest that hydroxyl groups at the C6 and C7 positions of the coumarin skeleton played an important role in the expression of tyrosinase inhibitory activity.
We attempted to determine whether docosahexaenoic acid (DHA)-induced apoptosis is mediated via the Bax-mediated pathway in human myeloid leukemia HL-60 cells. DHA-induced apoptosis was confirmed by morphological analysis and caspase-3 activation. But, cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition (MPT), did not inhibit DHA-induced Bax translocation to mitochondria or caspase-3 activation. These data suggest that DHA can induce apoptosis via the Bax-independent pathway.
CD9 antigen (p24) was purified from human platelets and partially characterized. The yield was 75 μg from 10 units of platelet concentrates. p24 (38 000 copies/platelet) has intramolecular disulfide bond(s) and, in SDS‐PAGE, consists of major 24‐kDa molecule and minor 26‐ to 31‐kDa molecules. The N‐terminal sequence of p24, PVKGOTKXIKYLLFGFNFIF, indicates that the protein has not previously been characterized and amino terminus (position 12–20) is hydrophobic.
